Trichomoniasis

Background

Trichomoniasis is a sexually transmitted infection (STI) caused by the motile parasitic protozoan Trichomonas vaginalis. It is one of the most common STIs, both in the United States and worldwide.^{[1, 2]}

The high prevalence of T vaginalis infection globally and the frequency of coinfection with other STIs make trichomoniasis a compelling public health concern. Research has shown that T vaginalis infection is associated with an increased risk of infection with several STIs, including gonorrhea, human papillomavirus (HPV), herpes simplex virus (HSV), and, most importantly, HIV.^{[1, 3, 4, 5]} Trichomoniasis is also associated with adverse pregnancy outcomes, infertility, postoperative infections, and cervical neoplasia.^[6]

T vaginalis may be transmitted vertically to newborns, causing vaginitis, urinary tract infection, and/or respiratory infection that can be life-threatening.^{[7, 8]}

Humans are the only known host of T vaginalis. Transmission occurs predominantly via sexual intercourse. The organism is most commonly isolated from vaginal secretions in women and urethral secretions in men. The rectal prevalence of T vaginalis among men who have sex with men (MSM) appears low.^[9] Although T vaginalis has not been isolated from oral sites, evidence suggests that it may cause sexually transmitted oral infection in rare cases.^[10]

Women with trichomoniasis may be asymptomatic or may experience various symptoms, including vaginal discharge and vulvar irritation. Men with trichomoniasis may experience nongonococcal urethritis but are frequently asymptomatic.^[11]

Trichomoniasis is thought to be widely underdiagnosed owing to various factors, including a lack of routine testing,^[2] the low sensitivity of a commonly used diagnostic technique (wet mount microscopy),^{[11, 12, 13]} and nonspecific symptomatology. Self-diagnosis and self-treatment or diagnosis by practitioners without adequate laboratory testing may also contribute to misdiagnosis. Currently, the Centers for Disease Control and Prevention (CDC) recommends numerous molecular detection methods to diagnose trichomoniasis, including several validated nucleic acid amplification tests (NAATs) and an antigen-detection test.^[11]

Testing for T vaginalis infection is recommended in all women seeking care for vaginal discharge, in addition to screening for T vaginalis in women at high risk of STI.^[11]

The CDC recommends two oral nitroimidazoles for the treatment of trichomoniasis: metronidazole (Flagyl) and tinidazole (Tindamax).^[11] Although generally more expensive, tinidazole is associated with fewer adverse effects than metronidazole and is equal or superior in resolving T vaginalis infection. When the first-line agent is ineffective (and reinfection by partner is ruled out), the other nitroimidazole or an alternative dosing schedule of metronidazole may be used. Topical metronidazole and other antimicrobials are not efficacious and should not be used to treat trichomoniasis.

Sexual partners of the infected patient should also be treated.^[11] Both the patient and partners should abstain from sexual activity until pharmacological treatment has been completed and they have no symptoms. In regions where expedited partner therapy (EPT) is legal, it may be useful in managing trichomoniasis.^[14] Infected women who are sexually active have a high rate of reinfection; thus, rescreening at 3 months posttreatment should be considered.^[11] Currently, data are insufficient to support rescreening men.

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Pathophysiology

T vaginalis trichomonads are approximately the size of white blood cells (about 10-20 μm long and 2-14 μm wide), although this may vary. Trichomonads have 4 flagella that project from the organism’s anterior and 1 flagellum that extends backward across the middle of the organism, forming an undulating membrane. An axostyle, a rigid structure, extends from the organism’s posterior.^{[15, 16]}

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Trichomonas vaginalis. (A) Two trophozoites of T vaginalis obtained from in vitro culture, stained with Giemsa. (B) Trophozoite of T vaginalis in vagi....

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Trichomoniasis overview.

In women, T vaginalis is isolated from the vagina, cervix, urethra, bladder, and Bartholin and Skene glands. In men, the organism is found in the anterior urethra, external genitalia, prostate, epididymis, and semen (see the image below). It resides both in the lumen and on the mucosal surfaces of the urogenital tract and uses flagella to move around vaginal and urethral tissues.^[16] T vaginalis has also been isolated from the rectum and detected via molecular techniques in the respiratory tract, although these are not common areas of infection.^{[10, 17, 9]} In cases of vertical transmission, T vaginalis may infect the respiratory systems of infants; however, little is known about this condition.^{[18, 19]}

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Life cycle of Trichomonas vaginalis. T vaginalis trophozoite resides in female lower genital tract and in male urethra and prostate (1), where it repl....

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Trichomoniasis life cycle.

T vaginalis destroys epithelial cells by direct cell contact and by the release of cytotoxic substances. It also binds to host plasma proteins, thereby preventing recognition of the parasite by the alternative complement pathway and host proteinases.^[1] During infection, the vaginal pH increases, as does the number of polymorphonuclear leukocytes (PMNs). PMNs are the predominant host defense mechanism against T vaginalis and respond to chemotactic substances released by trichomonads.^[1] The presence of antigen-specific peripheral blood mononuclear cells may also suggest that lymphocyte priming occurs during infection.^[16] Antibody response to T vaginalis infection has been detected both locally and in serum.

Despite the immune system’s interaction with T vaginalis, infection produces an immunity that is only partially protective at best, and there is little evidence that a healthy immune system prevents infection. One study showed no association between trichomoniasis and the use of protease inhibitors or immune status in HIV-infected women.^[20] Another showed that HIV seropositivity did not alter the rate of infection in males.^[21]

Symptoms of trichomoniasis typically occur after an incubation period of 4-28 days.^{[16, 22]} Infection generally persists for fewer than 10 days in males. The persistence of asymptomatic infection in women is unknown. Older women have been shown to have significantly higher rates of infection than younger women, which suggests that asymptomatic infection may persist for long durations in women.^{[23, 24]}

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Etiology

The risk of acquiring T vaginalis infections is based on engagement in high-risk sexual activity. Those who engage in the following sexual practices are at a greater risk for infection:

• New or multiple partners
• Exchanging sex for money or drugs
• Sexual contact with an infected partner
• Not using barrier protection

Several other factors may indicate a higher likelihood of T vaginalis infection but may not be directly or causally linked, as follows:

• A history of certain STIs
• Current STIs
• A history of injection drug use

Even if not directly causal, these factors may be predictive. In a study that considered risk factors for trichomoniasis, injection drug use in the preceding 30 days was the most strongly associated with infection and with new infection observed during the study.^[25]

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Epidemiology

United States statistics

Trichomoniasis is one of the most common STIs in the United States, with a prevalence estimated at 8 million cases annually; however, exact numbers are difficult to obtain because the infection is not nationally reportable and many infections are asymptomatic.^{[26, 27, 28, 29]} Prevalence is also thought to be underestimated owing to the low sensitivity of the commonly used wet mount technique.

Research in high-risk populations shows that the prevalence of trichomoniasis varies widely across the United States. In STI clinics, the prevalence of T vaginalis infection ranges from 15%-54%.^{[16, 30]} In 2 samples of female prison inmates, the prevalence was on the higher end of that range, between 31.2% and 46.9%.^{[31, 32]} In US men, trichomoniasis accounts for 10%-21% of urethritis cases not attributable to gonorrheal or chlamydial infection.^[30]

International statistics

The World Health Organization estimates the worldwide incidence of trichomonas infection at over 220 million cases, although the accuracy of this estimate is highly uncertain.^[33]

The incidence of trichomoniasis in Europe is similar to that in the United States. In Africa, the prevalence of trichomoniasis may be much higher. The prevalence of vaginal T vaginalis infection was estimated to be 11-25% among African study populations.^{[34, 35, 36]}

Age-related demographics

The National Longitudinal Study of Adolescent Health Study found a prevalence of 2.3% among adolescents aged 18-24 years and 4% among adults 25 years and older.^[37] A prevalence of 3.1% in females aged 14-49 years was observed based on a nationally representative sample of women in the National Health and Nutrition Examination Survey (NHANES) 2001-2004 study.^[38] Despite this trend, trichomoniasis is still a concern in younger women. In female adolescents, trichomoniasis is more common than gonorrhea; particularly disconcerting given that it increases susceptibility to other infections.^[39]

In a study of men attending an STI clinic in Denver, the prevalence of Trichomonas infection was 0.8% in men younger than 30 years and 5.1% in men 30 years and older.^[40] This increase in prevalence is believed to result from age-related enlargement of the prostate gland.

Vertical transmission of T vaginalis during birth is possible and may persist up to 1 year, causing UTI, and, less commonly, respiratory infection.^[10] Between 2% and 17% of female offspring of infected women acquire infection.^[41]

Sex-related demographics

Although both women and men can be asymptomatic or symptomatic carriers of T vaginalis, trichomoniasis in men tends to be less clinically apparent and of shorter duration. In addition, multiple studies have found that T vaginalis infection is less prevalent in men than in women.^{[40, 42, 43]} The NHANES 2001-2004 study conducted on a nationally representative sample of women aged 14-49 years found that 85% of women found to have trichomoniasis reported no symptoms.^[38]

The reported incidence of trichomoniasis among men in various populations ranges from 0.8%-17%.^{[40, 42]} This incidence may be underestimated, depending on the method of detection and the site of specimen collection. The use of multiple sites in the genitourinary tract (urine, urethral swab, and semen) in male patients has been shown to increase sensitivity.^[44] In one study, T vaginalis was detected in 72% of male sexual partners of women with trichomoniasis.^[45] Of these, 77% were asymptomatic.

Race-related demographics

In the National Longitudinal Study of Adolescent Health Study, significant differences in the prevalence of trichomoniasis among adolescents were noted by race: white, 1.2%; Asian, 1.8%; Latino, 2.1%; Native American, 4.1%; and African American, 6.9%.^[37] Considerable differences were also observed in the national NHANES 2001-2004 study conducted among women ages 14-49: non-Hispanic whites, 1.2%; Mexican Americans, 1.5%; and non-Hispanic blacks, 13.5%.^[38]

Evidence suggests that T vaginalis infection likely increases HIV transmission and that coinfection with HIV complicates treatment of trichomoniasis.^[46] Control of T vaginalis may represent an important means of slowing HIV transmission, particularly among African Americans, in whom higher rates have been observed.

Daugherty et al screened a representative sample of men aged 18-59 years with RNA testing for T vaginalis and found that 0.49% were infected.^[47]

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Prognosis

Trichomoniasis can usually be treated quickly and effectively. Single-dose metronidazole regimens have produced a 90%-95% cure rate in randomized clinical trials, while single-dose tinidazole regimens have produced cure rates of 86%-100%.^[48] Recurrent infections are common in sexually active patients. One study found that 17% of sexually active patients with T vaginalis infection were reinfected at 3-month follow-up.^[49] Multiple randomized trials have found that this rate of reinfection can be significantly reduced through expedited partner therapy.^{[50, 51]}

T vaginalis infection is also strongly associated with the presence of other STIs, including gonorrhea,^[52] chlamydia, and sexually transmitted viruses. T vaginalis infection has even been shown to increase a patient’s susceptibility to sexually transmitted viruses, including herpes simplex virus, human papillomavirus, and HIV.^{[39, 46]} Persons with trichomoniasis are twice as likely to develop HIV infection as the general population.^[35] One potential explanation for this is that T vaginalis disrupts the epithelial monolayer, leading to increased passage of the HIV virus.^[53] Another posits that T vaginalis induces immune activation, specifically lymphocyte activation and replication and cytokine production, leading to increased viral replication in HIV-infected cells.^[54] Further research is needed to clarify the exact mechanism by which T vaginalis increases the risk of HIV infection.

Women may experience various complications associated with trichomoniasis. One study reported a higher risk of pelvic inflammatory disease in women with trichomoniasis.^[55] Other studies have reported a 1.9-fold risk of tubal infertility in women with trichomoniasis.^[56] Trichomoniasis may also play a role in cervical neoplasia and postoperative infections.^[6]

Pregnant women with T vaginalis infection are at an especially high risk for adverse outcomes, which may include the following:

• Preterm delivery
• Low birth-weight offspring
• Premature rupture of membranes
• Intrauterine infection^[1]
• Respiratory or genital T vaginalis infection in the newborn^[11]

T vaginalis infection may also increase the likelihood of vertical HIV transmission owing to disruption of the vaginal mucosa.^[11]

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Patient Education

Education concerning STI treatment and prevention is vital (see Prevention). Because T vaginalis infection is strongly associated with the presence of other STIs (gonorrhea,^[52] chlamydia, and sexually transmitted viruses such as HIV), providers should provide appropriate counseling, testing, and treatment for such infections.

Upon diagnosis of trichomoniasis, healthcare providers should discuss treatment, including the adverse effects and interactions encountered with metronidazole and tinidazole. It is especially important to warn patients to abstain from alcohol when taking metronidazole and tinidazole. Providers should also address the treatment of sexual partners and, where allowed by law, employ expedited partner therapy. Individuals with trichomoniasis who notify partners of their infection help disrupt the transmission of trichomoniasis and other STIs.^[57]

Providers should also discuss methods of preventing T vaginalis reinfection. It may be important to explain that T vaginalis infection may be longstanding and not due to a recent sexual encounter.

The CDC advises providers to consider rescreening sexually active women at 3 months after the completion of treatment.^[48] Currently, the CDC makes no recommendation regarding the rescreening of sexually active men, but it may be desired if reinfection is likely.^[11]

The CDC does not take a definitive stance on treating trichomoniasis during pregnancy. Studies have shown both positive and negative outcomes of treatment with a single 2-gram dose of metronidazole. Physician discretion is advised.^[11] See the patient education fact sheet below.

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Patient education fact sheet on trichomoniasis.

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History

T vaginalis transmission occurs predominantly via sexual intercourse, so it is typically found in sexually active individuals. The organism is most commonly isolated from vaginal secretions in women and urethral secretions in men. Rectal prevalence of T vaginalis among men who have sex with men appears low.^[9] Although T vaginalis has not been isolated from oral sites, evidence suggests that it may cause a sexually transmitted oral infection in rare cases.^[17] T vaginalis is also transmitted vertically^[58] and can be asymptomatic for long durations. Nearly half of infected females and nearly all infected males are asymptomatic.^{[22, 59]} One third of asymptomatic women become symptomatic within 6 months.^[22] Because of this, a lack of sexual history should not be used to rule out T vaginalis infection as a possible diagnosis.

Women

Trichomoniasis symptoms in women range from none to severe pelvic inflammatory disease (PID). Women with trichomoniasis frequently report an abnormal vaginal discharge, which may be purulent, frothy, or bloody. Although frothy vaginal discharge is thought to be the classic presentation of trichomoniasis, women with trichomoniasis also commonly report the following:^{[16, 60]}

• Abnormal vaginal odor (often described as musty)
• Vulvovaginal itching, burning, or soreness
• Dyspareunia (pain during sexual intercourse), often the major complaint
• Dysuria (pain during urination)
• Postcoital bleeding
• Lower abdominal pain

In addition to its associated signs and symptoms, trichomoniasis may lead to cervicitis. This is characterized by 2 major signs, as follows:^[57]

• Purulent discharge in the endocervical canal
• Easily induced endocervical bleeding

T vaginalis infection is also one of the top 3 causes of vaginitis.^[57] Vaginitis is usually characterized by vaginal discharge presenting with any of the following:

• Vulvar itching
• Irritation
• Odor

The two other most common causes of vaginal discharge are anaerobic bacterial overgrowth of normal flora and candidiasis (infection with Candida albicans).^[57]

Men

Men with trichomoniasis may be asymptomatic, may have mild symptoms, or may experience acute trichomoniasis. Men with trichomoniasis are more likely than women to be asymptomatic and tend to have much faster natural disease resolution.

Trichomoniasis symptoms in men range from none to urethritis complicated by prostatitis. Nongonococcal nonchlamydial urethritis is the most common symptom reported by men with trichomoniasis. Symptoms of urethritis include the following:^[57]

• Discharge (purulent to mucoid in character)
• Dysuria
• Urethral pruritus

Less-common symptoms may include the following:

• Pain in the urethra
• Testicular pain
• Lower abdominal pain

Most symptomatic T vaginalis infections in men are intermittent and self-limiting.

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Physical Examination

Women

Vaginal discharge is found in 42% of women with trichomoniasis.^[16] The discharge is classically described as thin and frothy; however, this is only seen in about 12% of patients.^[16] The discharge is often yellow and is sometimes viscous enough to be confused with candidiasis. Abnormal vaginal odor was found in approximately half of infected women, and edema or erythema was found in 22%-37%.^[16] Vaginal pH is often elevated (>4.5).^[61]

One of the classic signs of ​T vaginalis infection is colpitis macularis, or strawberry cervix, which describes a diffuse or patchy macular erythematous lesion of the cervix. This is a specific sign of trichomoniasis but is visible in only 1%-2% of cases without the aid of colposcopy; with colposcopy, colpitis macularis is detected in up to 45% of cases.^[52] Together, colpitis macularis and frothy vaginal discharge have a specificity of 99%; individually, they have positive predictive values of 90% and 62%, respectively.

Lower-abdominal tenderness may be present, although this is described in fewer than 10% of patients. If this occurs, coexisting salpingitis or an intra-abdominal pathology is possible.

Coexisting Neisseria gonorrhoeae infection, candidiasis, and bacterial vaginosis are common and may produce a mixed clinical picture.

Most of the symptoms described above are not specific for trichomoniasis and can occur in other vaginal or cervical infections. In one study, the clinician’s ability to accurately diagnose T vaginalis infection on the basis of physical findings alone had a positive predictive value of only 47%.^[62] Relying on physical examination findings alone misses the diagnosis of most patients with trichomoniasis. Definitive diagnosis requires appropriate laboratory testing.

Men

Most men with trichomoniasis have no physical findings. Infrequently, infected men have abnormal penile discharge. However, the discharge usually is only scant and thin. Trichomoniasis in men may be associated with local inflammatory states, including balanitis and balanoposthitis. Epididymitis and prostatitis may also be present.^[63]

Children

In female newborns, T vaginalis acquired during birth may cause vaginal discharge during the first week of life. Respiratory infection in newborns is also possible.^[48] An infected infant may present with fever.

Prepubertal children with trichomoniasis may present with symptoms similar to those seen in the adolescent and adult patient. T vaginalis infection in prepubertal children may suggest sexual abuse but may also arise from earlier vertical transmission.

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Complications

In women, vaginitis is the most common manifestation of infection. Other complications include cervicitis and infection of the adnexa, endometrium, and Skene and Bartholin glands. Pelvic inflammatory disease and tubo-ovarian abscess may also occur.

In symptomatic men, T vaginalis infection usually manifests as urethritis. As many as 11% of nongonococcal urethritis cases in men are caused by T vaginalis.^[64] Complications of untreated trichomoniasis in men include prostatitis, epididymitis, urethral stricture disease, and infertility, potentially resulting from decreased sperm motility and viability.^{[6, 65]}

Research has shown T vaginalis infection increases the risk of HIV transmission in both men and women.^{[3, 1]} It is estimated that, in women alone, 747 new HIV cases per year result from the facilitative effects of T vaginalis on the transmission of HIV.^[66] Overall, persons with trichomoniasis are twice as likely to develop HIV infection as the general population.^[35] Symptomatic men with comorbid T vaginalis and HIV infections have been found to have significantly higher numbers of HIV RNA particles in their seminal fluid.^[3] Treatment of trichomoniasis has been shown to decrease the rate of viral shedding in patients with HIV infection.^{[3, 67]}

In addition to HIV, T vaginalis infection also increases the susceptibility to other viruses, including herpes and human papillomavirus (HPV). T vaginalis may increase the rate of infection or reactivation of HPV, although it may also shorten the duration of infection.^[68]

The following disorders have also been associated with trichomoniasis:

• Cervical intraepithelial neoplasia^[69]
• Posthysterectomy infection, including cuff cellulitis, cuff abscess, and wound infection^[70]
• Trichomonal peritonitis (rare)^[71]

In pregnant women, T vaginalis infection has been associated with an increased risk of low birth weight, preterm delivery, and intrauterine infection.^{[72, 1]} Neonatal trichomoniasis, usually presenting as a genital infection, has been described.^[19] Rarely, trichomoniasis presents as a serious respiratory infection.^[11]

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Approach Considerations

Given the poor reliability of history and physical findings, diagnosis of trichomoniasis depends on laboratory testing. According to the CDC, providers should perform laboratory tests for trichomoniasis in all women seeking care for vaginal discharge and all women at high risk of STIs.^[48]

Tests for trichomoniasis are quick and can be performed in the medical office.^[73] In the past, saline wet mount testing was commonly used to test for trichomoniasis, although these tests have low sensitivity. The CDC now recommends molecular diagnostic tests, when available, to evaluate patients at risk for trichomoniasis.^[11] Self-testing has also been proposed and studied but is not currently approved by the US Food and Drug Administration (FDA).^{[74, 75]}

The basic office evaluation includes tests to exclude other possible causes of the patient’s complaints. Because T vaginalis infection is strongly associated with the presence of other STIs,^[52] providers should test for other STIs, including gonorrhea, chlamydia, syphilis, HIV infection, hepatitis B, and hepatitis C. In multiple studies, the majority of women with T vaginalis infections were also found to have bacterial vaginosis.^{[76, 77, 52]}

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Standard Laboratory Studies

Molecular Techniques for Detecting Antigen, DNA, or RNA

The following six FDA-approved molecular tests are currently available for diagnosing trichomoniasis in women:

• Affirm VPIII Microbial Identification Test (a DNA probe; BD Diagnostic Systems, Sparks, Maryland)
• APTIMA T vaginalis assay (a nucleic acid hybridization test, Hologic Gen-Probe, San Diego, California)
• BD ProbeTec TV Qx Amplified DNA Assay (a DNA probe, Becton Dickinson, Franklin Lakes, New Jersey)
• OSOM Trichomonas Rapid Test (an antigen-based test; Genzyme Diagnostics, Cambridge, Massachusetts)
• Solana Trichomonas Assay (a DNA probe, Quidel, San Diego, California)
• Xpert TV Assay (a DNA probe, Cepheid, Sunnyvale, California)

All the above tests have a sensitivity greater than 83% (except for the Affirm VPIII, at 63%) and a specificity greater than 97% for detecting T vaginalis in vaginal secretions. Of the above tests, only Xpert TV has been FDA-approved for the diagnosis of trichomoniasis in men.^[78] However, according to the CDC, APTIMA may also be used with male urine or urethral swabs from men.^[11]

Affirm VPIII Microbial Identification Test

The Affirm VPIII Microbial Identification Test detects the presence of Trichomonas, Gardnerella, and Candida species by using direct hybridization technology. Its sensitivity is 90%-100%,^[79] and the detection threshold is reported to be 5,000 trichomonads/mL. Results from the Affirm VPIII test are available within about 45 minutes.

A bulletin on proper preparation and testing of specimens is available from the manufacturer. Specimens for which testing is expected to be delayed for more than 1 hour at ambient temperature or 4 hours with refrigeration should be stored in the Affirm VPIII Ambient Temperature Transport System (ATTS) for up to 72 hours.^[80] In a study by Hollman et al, no difference was noted in detection of T vaginalis in urine samples compared with vaginal swabs.^[81]

APTIMA Trichomonas Vaginalis Assay

The APTIMA Trichomonas vaginalis Assay (Gen-Probe, San Diego, Calif) uses nucleic acid hybridization technology to detect the presence of T vaginalis.^{[57, 82]} Sensitivity is 74%-98%, and specificity is 87%-98%.^[38] One study reported decreased sensitivity for tests performed on first-void urine specimens in male patients.^[79] The sample is run on a proprietary processing system capable of running about 1,000 samples per day. Expected turnaround time is about 1-2 days. Currently, the APTIMA Combo2 assay is FDA-approved for the diagnosis of chlamydia and gonorrhea, so laboratories using this technology may wish to add the T vaginalis assay to their existing technology.

BD ProbeTec TV Qx Amplified DNA Assay

The BD ProbeTec TV Qx Amplified DNA Assay is a DNA-amplification test developed for the BD Viper system, a proprietary automated platform capable of testing for T vaginalis, Chlamydia trachomatis, N gonorrhoeae, HSV-1, and HSV-2.^[83] Sensitivity for the assay using self-collected vaginal swabs is 98.3% and specificity is 99%, compared with a composite reference standard of wet mount microscopy and culture.^[78] The system can run 96 samples per batch.^[83] An independent evaluation of the system found that samples can be run with between 78.7 and 81.2 minutes of total processing time and only 29.8 and 34.2 minutes of “hands-on” laboratory work.^[84]

OSOM Trichomonas Rapid Test

The OSOM Trichomonas Rapid Test uses color immunochromatographic “dipstick” technology with murine monoclonal antibodies. Results are read within 10 minutes. Freezing and transportation of specimens do not appreciably alter the test results. In a comparison with a composite reference standard of wet mount microscopy and culture, Huppert et al found the sensitivity of the OSOM test to be 83.3% and the specificity 98.8%.^[85] A second study by Huppert et al found a sensitivity of 82% in comparison with a composite reference standard of wet mount, culture, rapid antigen testing, and polymerase chain reaction (PCR).^[86] A third study compared the OSOM test to a composite reference standard for which a positive sample was defined as one that was positive by any combination of wet mount, Aptima ATV assay, or OSOM test. The prevalence of infection in the population tested was low, at 2%. The sensitivity was 94.7%, and the specificity was 100%.^[87]

Solana Trichomonas Assay

The Solana Trichomonas Assay is a relatively rapid point-of-care assay that uses isothermal helicase-dependent amplification to amplify and identify T vaginalis DNA present in vaginal swabs and urine samples of female patients.^[88] Results can be read within 40 minutes. Gaydos et al found that the sensitivity of the Solana assay compared to the Aptima-TV assay was 89.7% for swabs and 100% for urine samples.^[89] The same study found that the specificity of the Solana assay was 99% for swabs and 98.9% for urine samples.^[89]

Xpert TV Assay

The Cepheid Xpert TV Assay is a DNA amplification assay developed for the Cepheid GeneXpert System, a proprietary automated cartridge platform capable of performing diagnostic tests for a wide variety of infectious agents, including T vaginalis, C trachomatis, N gonorrhoeae, influenza, group B Streptococcus, and Clostridium difficile.^[90] The assay is unique among currently available nuclear amplification assays in that it is validated by the FDA for use with male urine samples.^[91] An independent evaluation of the Xpert TV Assay compared the test to a combination of APTIMA TV Assay and InPouch TV broth culture. This clinical review of the Xpert TV Assay found that the test had a sensitivity ranging between 99.5% and 100% for all female samples (including swabs, urine samples, and self-collected vaginal swabs) and a specificity ranging between 99.4% and 99.9%.^[91] For male urine samples, the assay had a sensitivity of 97.2% and a specificity of 99.9%.^[91]

According to the manufacturer, the Xpert TV Assay has a total “hands-on” time of 1 minute, and first results are available within 40 minutes.^[90]

Other Molecular Techniques

PCR methods yield a high sensitivity (84%) and specificity (94%).^{[92, 93]} PCR is based on DNA amplification and detection using known primers to TV genes. Because no approved PCR tests are available for general use, this approach is limited to research studies. Sensitivities of PCR tests for T vaginalis have been reported at 85-100%.^{[2, 94, 95]} Amplicor, an FDA-approved PCR assay for gonorrhea and chlamydia modified to detect T vaginalis, was found to have a sensitivity of 88%-97% and specificity of 98%-99%.^[96] Some researchers have suggested that PCR has great diagnostic potential,^[30] particularly in men, while others maintain it offers little advantage over culture. In men, performing PCR on urine sediment rather than urethral swabs may improve detection rates.^[97]

Direct fluorescent antibody (DFA) staining is more sensitive than saline wet mount but less sensitive than culture. DFA allows rapid diagnosis but requires a trained microscopist and a fluorescent microscope.

Saline wet mount evaluation

In women, vaginal trichomoniasis has historically been diagnosed via wet mount microscopy, which has very low sensitivity (25%) for detecting T vaginalis compared with most molecular tests.^[98] Although it is not the criterion standard technique for trichomoniasis diagnosis, wet mount is frequently used because it is quick, inexpensive, and easy to perform.^{[57, 12, 13]} The absence of trichomonads on microscopy does not rule out a diagnosis of vaginal trichomoniasis. Because they involve the direct visualization of the trichomonads, wet mounts are more likely to return positive results in women with high organism loads.^[2] Wet mount microscopy is not an effective test for the diagnosis of trichomoniasis in men. Saline wet mount evaluation is performed by placing a small amount of vaginal discharge on a microscope slide and mixing with a few drops of saline solution. The slide is then examined under a microscope at low or medium power. See the video below.

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Trichomonas vaginalis on a saline wet mount at 40X on the microscope. Several motile parasites transit through the field, surrounded by white blood cells and squamous epithelial cells.

The presence of flagellated pyriform protozoa, or trichomonads, indicates a positive test result. These ovoid-shaped parasites are slightly larger than polymorphonuclear leukocytes (PMNs), a type of white blood cell, and may be identified by their ameboid mobility. Trichomonads cause an inflammatory reaction; therefore, a large number of PMNs are usually present and correlate with the severity of infection.

Slides must be read immediately after collection.^[57] Kingston et al looked at samples that were positive for trichomonads on initial reading and then reevaluated them every 10 minutes.^[99] At 10 minutes, 20% of samples became negative; by 30 minutes, 35% were negative; and by 2 hours, 78% had become negative.

The relatively poor sensitivity of saline wet mount evaluation may be increased somewhat by using cervical vaginal lavage.^[100] In one study, sensitivity was increased to 74.4% using the cervical vaginal lavage technique versus 54.7% vaginal swab alone.^[100]

A short downloadable video illustrating this test is available from the Seattle STD/HIV Prevention Training Center.^[101]

Standard culture

Culture was the criterion standard for trichomoniasis diagnosis before the introduction of molecular testing techniques. Culture is more sensitive and specific than microscopy but similar in both respects to molecular testing techniques.^{[57, 102]} Providers may perform T vaginalis cultures when the suspicion of trichomoniasis is high but other tests do not reveal the protozoan. Culture has also been demonstrated to be useful in individuals with suspected resistant trichomoniasis, as providers can obtain the drug susceptibility of the strain. In addition, culture may be useful as diagnostic screening in high-risk populations.^[16]

Disadvantages of culture include testing time and availability.^[30] The CDC does not recommend oral and rectal testing, as infection rates at these sites appear to be low.^[48]

In order to perform culture, a swab is put in broth and incubated anaerobically at 37°C. Growth is usually detected within 48 hours, and samples without growth after 7 days are considered negative for trichomoniasis.^[102]

InPouch TV Culture System

The InPouch TV Culture System (Biomed, White City, Oregon), a combined wet mount and culture kit, is commonly used and readily available. This test kit has a sensitivity of 81%-100% and may detect as little as 1 parasite in the sample.^[103]

The clinician inoculates the upper chamber of the pouch with a cotton swab. The pouch can be kept at room temperature for up to 18 hours without significant alteration of sensitivity. In the laboratory, a viewing clamp is placed across the upper chamber and examined under a microscope at a magnification of 100. If no trichomonads are viewed, the bottom chamber is inoculated by using the medium from the upper chamber. The InPouch is incubated at 37°C and viewed at regular intervals.

Nonspecific Laboratory Tests

Papanicolaou Smear

Trichomonads may be viewed on Pap smear, but this test yields low sensitivity and should not be relied on for diagnosis of T vaginalis infection. The sensitivity of Pap smear for detecting trichomonads is 40-60%.^{[104, 105]} Specificity approaches 95% in the hands of trained technicians.^[106] False-positive results are also common with this technique.^[30]

Whiff Test (amine odor test)

A whiff test is performed by adding several drops of 10% potassium hydroxide to a sample of vaginal discharge. A strong fishy odor is indicative of a positive test result. Such a result may suggest either trichomoniasis or bacterial vaginosis. Thus, the whiff test should not be considered an accurate means of diagnosing trichomoniasis. It is 1 of the 4 parts of the Amsel criteria used to diagnose bacterial vaginosis.^[107]

The whiff test is now combined with vaginal pH on a single card; the FemExam pH and Amines TestCard. On this card, the pH paper color change and the odor test are replaced with plus or minus signs.

pH Testing

Vaginal pH may be determined by touching a swab containing vaginal secretions to pH indicator paper. A normal pH practically excludes the diagnosis of symptomatic trichomoniasis. A pH greater than 4.5 is usually found with trichomoniasis.^[61] However, an elevation in pH is not specific for trichomoniasis.^[57]

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Approach Considerations

Evaluation for trichomoniasis is typically conducted in the outpatient setting. Trichomoniasis is not a nationally mandated reported sexually transmitted disease, although other sexually transmitted disease reporting requirements vary by state.^[11]

After positive diagnosis, treatment should be instituted immediately and, whenever possible, in conjunction with all sexual partners.^[11] Expedited partner therapy is a safe and effective means of treating the sexual partners of patients diagnosed with trichomoniasis and should be practiced whenever possible.^{[108, 46, 50]} Both patient and partner should abstain from sex until pharmacological treatment has been completed and they have no symptoms.

Patients undergoing pharmacotherapy should be advised to avoid alcohol consumption during the course of treatment and for an appropriate amount of time after the completion of their medication.

Because trichomoniasis is an infection of multiple sites (eg. vaginal epithelium, Skene glands, Bartholin glands, and urethra), systemic treatment is needed. Because of the high rate of coinfection with other sexually transmitted infections (STIs), the healthcare provider should consider empiric treatment of gonorrhea and chlamydia. Patients should also be offered counseling and testing for HIV.

In clinical practice, repeat testing is rarely performed unless symptoms do not improve with drug treatment. However, the CDC recommends rescreening at 3 months posttherapy for sexually active women, as they have a high rate of reinfection.^[96] Currently, no data are available on rescreening men.

Inpatient therapy is usually not required but may be indicated when resistance is present and intravenous (IV) therapy is indicated. For patients in whom treatment fails and in whom reinfection is ruled out, consultation with experts from the CDC may be advisable (770-488-4115). Consultation with an infectious diseases specialist, a gynecologist, or both may be helpful.

HIV

Patients who are HIV-positive should generally receive the same treatment as those who are HIV negative. The notable exception is that the multiday treatment drug regimen (metronidazole 500 mg twice daily for 7 days) was recently shown to be more effective in treating T vaginalis in HIV-positive women than a single-dose treatment (metronidazole 2 g single dose).^[109] Thus, the CDC recommends considering the multidose treatment in HIV-positive women with trichomoniasis.^[48] The CDC also recommends rescreening at 3 months after the completion of therapy for HIV-positive women due to the likelihood of recurrent or persistent infection and the increased risk of HIV transmission with comorbid trichomoniasis.^{[48, 49, 110, 111]}

Pregnancy

Although the CDC does not take a definitive stance on treating trichomoniasis during pregnancy, it recommends a single 2-g dose of metronidazole if treatment is deemed necessary. One study has found an association between the use of metronidazole during pregnancy and premature delivery, but this result has not been reproduced by other studies.^[112] Treatment of trichomoniasis during pregnancy may relieve symptoms of vaginal discharge or prevent the rare complication of neonatal respiratory infection with trichomoniasis.^[11] Vertical transmission of trichomoniasis during delivery is relatively rare, but respiratory or genital infection of the newborn during delivery has been reported.^[48]

Infected asymptomatic pregnant women may wish to defer treatment to after 37 weeks’ gestation.^{[48, 11]}

In breastfeeding women, the CDC recommends stopping breastfeeding during the course of metronidazole treatment and for 12-24 hours after the last day. For treatment with tinidazole, the CDC recommends stopping breastfeeding for the course of treatment and for 3 days after the last dose.^[48]

Treatment of pregnant women with tinidazole has not been well-studied, however animal studies suggest that the drug poses moderate risks. Use of tinidazole is not recommended in pregnant women.^[11]

Pediatric populations

T vaginalis infection in a pediatric patient may suggest child abuse, although vertical transmission is also a possibility. Young girls may present with vaginal discharge.

Routine screening for trichomoniasis in asymptomatic pregnant women is not currently recommended.

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Pharmacologic Therapy

5-Nitroimidazole drugs are the only widely used pharmacological treatment for trichomoniasis. In the United States, two of these drugs, metronidazole and tinidazole, are FDA-approved. The CDC recommends the following drug schedules in the treatment of trichomoniasis:^[11]

• A single 2-g dose of metronidazole
• A single 2-g dose of tinidazole
• A schedule of 500 mg of metronidazole, taken twice daily for 7 days

Each drug schedule has advantages and disadvantages, but, ultimately, they yield similar cure rates. In a 2003 Cochrane review, metronidazole and tinidazole had comparable efficacy in treating trichomoniasis.^[1] Randomized clinical trials comparing single 2-g doses have also shown metronidazole and tinidazole to be equally effective.^[11] With recommended dosages, the expected cure rate of trichomoniasis is 95%. Tinidazole is generally more expensive than metronidazole but also seems to persist in serum longer.^[11] Some research suggests that tinidazole has fewer side effects than metronidazole, but not all studies have found this result.^{[1, 113, 114]}

The advantages of single-dose therapy with metronidazole or tinidazole over the week-long metronidazole schedule include better patient compliance and a lower total dose. The week-long metronidazole schedule may be more effective in treating trichomoniasis in HIV-infected women.^[109]

Because trichomoniasis is an infection of multiple sites, systemic (oral) treatment is needed. Topical medications are not recommended by the CDC, as they are unlikely to reach therapeutic levels. Topical metronidazole and other antimicrobials yield low cure rates (< 50%).^[11]

The mechanism of action for these drugs is not completely understood. It is thought that target organisms preferentially reduce the 5-nitro group on the molecule, creating active metabolites that disrupt the helical structure of DNA. This prevents nucleic acid synthesis and eventually leads to cell death.^[115]

For both metronidazole and tinidazole, patients should not consume alcohol during the course of treatment, as nitroimidazoles can create a disulfiram-like intolerance reaction when taken with alcohol.^[116] Among those on metronidazole therapy, abstinence should continue for 24 hours after the last dose. Among those on tinidazole therapy, abstinence should continue for 72 hours after completion of the medication.^[48] Treating the patient’s sexual partners to prevent reinfection further improves the cure rate. Where legal, this may be easier to accomplish with expedited partner therapy.^[14]

Despite the widespread use of nitroimidazoles in the treatment of trichomoniasis, resistance to these drugs is rare and is typically solved by increasing the dose or switching to another nitroimidazole.^[1] The CDC has reported incidents of trichomoniasis resistant to metronidazole that were susceptible to tinidazole.^{[117, 118]} When standard treatment regimens fail, a regimen of 2 g of oral metronidazole or tinidazole for 5 days may be considered.^[57] Inpatient intravenous (IV) therapy may be indicated when resistance is present.

For patients in whom treatment fails and in whom reinfection is ruled out, consultation with experts from the CDC may be advisable (770-488-4115). Consultation with an infectious diseases specialist, a gynecologist, or both may be helpful.

Patients allergic to this class of drug should be referred to an allergist for desensitization.

Metronidazole

Before the introduction of tinidazole, metronidazole was the treatment of choice for trichomoniasis. Metronidazole is typically administered as either a single-dose therapy taken with food or a 500-mg therapy taken twice daily with food for 7 days. Single-dose therapy is as effective as prolonged therapy, although single-dose therapy causes slightly fewer side effects and increases drug adherence.^[11]

The 7-day schedule of metronidazole therapy may be more effective in treating trichomoniasis in women with HIV infection and should be considered in this population.^[109] A modified 7-day schedule (400 mg 3 times a day) should be considered in breastfeeding women.^[11] Studies suggest that this schedule produces a lower concentration of metronidazole in breast milk over longer periods.^{[119, 120]}

Treatment failure with single-dose metronidazole therapy increased from 0.4% to 3.5% between 1999 and 2002.^[121] Reports now describe resistance to metronidazole approaching 5%-10%. If standard treatment with either single-dose or multidose therapy fails, a regimen of 2 g of oral metronidazole or tinidazole for 5 days may be considered.^[11]

Metronidazole gel is effective in less than 50% of trichomoniasis cases and is not recommended to treat trichomoniasis.^[122]

Patients should not consume alcohol during the course of treatment or during the 24 hours after the completion of the medication.^[48]

Metronidazole in Pregnancy

Metronidazole crosses the placenta in pregnancy and is considered a pregnancy Class B agent by the FDA. A number of clinical trials and meta-analyses have not shown it to have teratogenic effects.^{[122, 123]} The National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network presented data suggesting that metronidazole treatment of asymptomatic carriers of T vaginalis increased the risk of preterm birth.^{[124, 125]} This was a controversial conclusion in that the investigators treated T vaginalis infection with 4 doses of 2 g metronidazole, which is significantly more than what is standard practice. The women included in the study were between 16 and 23 weeks’ gestational age, suggesting a significant delay in treatment. A subsequent study by Mann et al showed no increased risk of preterm birth with the use of metronidazole for the treatment of trichomoniasis.^[126]

Although the CDC does not take a definitive stance on treating trichomoniasis during pregnancy, it recommends a single 2–g dose of metronidazole if treatment is deemed necessary.^[11] Treatment of trichomoniasis during pregnancy may relieve symptoms of vaginal discharge or prevent the rare complication of neonatal respiratory infection with trichomoniasis. Treatment has not been shown to reduce the incidence of preterm-delivery associated with T vaginalis infection.^[11] Vertical transmission of trichomoniasis during delivery is relatively rare, but respiratory or genital infection of the newborn during delivery has been reported.^[8] Infected asymptomatic pregnant women may wish to defer treatment until after 37 weeks’ gestation.^[48]

Tinidazole

Like metronidazole, tinidazole is typically given as a single-dose therapy of 2 g taken with food. Randomized clinical trials comparing single 2-g doses have shown metronidazole and tinidazole to be equally effective.^[11] Cure rates range from 86%-100%.^[48] Tinidazole has a longer half-life (12-14 hours) than metronidazole (6-7 hours). For resistant infections, some recommend using 2 g twice daily for 14 days.^[118]

Patients on tinidazole therapy should not consume alcohol during therapy or for 72 hours after completion of the medication.^[48]

Tinidazole in Pregnancy

Tinidazole should not be used in pregnant women, as it is a pregnancy class C agent. Animal studies have demonstrated adverse effects on fetal development.^[11]

In lactating women, it is recommended that breastfeeding be withheld during treatment and for 3 days after the last dose.^[11]

Clotrimazole

The CDC does not currently recommend the use of clotrimazole for treatment of trichomoniasis. Clotrimazole vaginal tablets have been used in the past; however, in a study by duBouchet et al, the cure rate was only 11% with this mode of therapy.^[127]

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Diet and Activity

Patients should be instructed to avoid alcohol while taking metronidazole, tinidazole, or other nitroimidazole drugs. The interaction of these drugs with alcohol may cause a disulfiram-like reaction.^[128]

Modifying sexual behavior helps reduce the incidence of infection. Patients should avoid sex until drug therapy is completed and all symptoms have disappeared.^[57] Treatment of the patient’s partner is crucial for minimizing reinfection. Thereafter, consistent use of condoms and other barrier contraceptives reduces the chance of infection. (See Prevention.)

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Prevention

Abstinence from sexual intercourse prevents trichomoniasis, except in cases of vertical transmission. Male condoms are the best and most reliable protection against T vaginalis transmission during intercourse.^[129] Limiting the number of sexual partners and using diaphragms have been shown to protect against the transmission of trichomoniasis.^[38] Although the efficacy of female condoms is undefined, they may also provide some protection from T vaginalis infection.^{[57, 11, 130]}

Spermicides that contain nonoxynol-9 may decrease the risk of trichomoniasis^[131] , although frequent use may be associated with an increased risk of HIV infection and other sexually transmissible agents owing to the disruption of the genital epithelium. The CDC does not recommend the use of nonoxynol-9 spermicides for the prevention of trichomoniasis.^{[57, 11]}

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Long-Term Monitoring

Infected women who are sexually active have a high rate of reinfection. Rescreening sexually active women at 3 months posttreatment has been reviewed and studied and is recommended.^{[48, 132]} Evidence is currently insufficient to support a similar recheck in male patients, but it may be undertaken at physician discretion.

Because trichomoniasis has a high rate of comorbidity with other STIs, providers should consider empiric treatment of infections that frequently coexist with trichomoniasis, such as gonorrhea and chlamydia. Patients should be advised to follow up on results of other studies performed.

If symptoms persist despite pharmacotherapy, patients should follow up with their primary care providers. Persistent treatment failures may require metronidazole susceptibility testing through the CDC.

Sexual partners of patients infected with trichomoniasis must be treated to prevent reinfection. Patient and sexual partners should abstain from sexual intercourse until they have both completed therapy and are asymptomatic.^[57] In areas where it is legal, expedited partner therapy may be useful in efficiently treating all sexual partners of the patient.^[14]

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Medication Summary

The following treatment options are recommended by the CDC:

• Single-dose 2-g oral metronidazole therapy
• Prolonged metronidazole therapy with 500 mg twice daily for 7 days
• Single-dose 2-g oral tinidazole therapy

Single-dose tinidazole or metronidazole appears to be equally effective in the treatment of trichomoniasis. Tinidazole is generally more expensive than metronidazole but may have fewer side-effects and remains in serum longer. Single-dose therapy with metronidazole or tinidazole improves patient compliance and results in a lower total dose than the week-long metronidazole schedule, although the week-long schedule may be useful in some situations, such as in patients with HIV infection or those who are breastfeeding.^[11] Topical treatments are not recommended due to inadequate therapeutic levels.^[11] Treatment with oral metronidazole has not been shown to have teratogenic effects^{[122, 123]} and may prevent transmission to the infant. The CDC does not offer a definitive recommendation on treating pregnant patients with symptomatic trichomoniasis but currently recommends that a single 2-g dose of metronidazole be used when treatment is prescribed.^[11] Infected asymptomatic pregnant women may wish to defer treatment to after 37 weeks’ gestation.^[48] Tinidazole is a pregnancy Class C agent and should not be used by pregnant women.

Drug-resistance in T vaginalis infection is rare, despite the prevalent use of nitroimidazole drugs. Treatment failures may require a higher-dose regimen, a longer course of the agent, or the use of different nitroimidazoles. In cases of resistance, nimorazole, ornidazole, furazolidone, ornidazole, and hamycin have been used with success.^[117]

Consultation with CDC experts may be advisable for patients in whom treatment fails and in whom reinfection is ruled out (770-488-4115). Consultation with an infectious diseases specialist, a gynecologist, or both may be helpful.

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Metronidazole (Flagyl)

• Dosing, Interactions, etc.

Clinical Context:  Metronidazole is highly effective in the treatment of many anaerobic bacterial and protozoal infections. Oral metronidazole is the drug of choice for trichomoniasis. Single-dose therapy with 2 g orally is as effective as prolonged therapy with 500 mg twice daily for 7 days. Single-dose therapy increases compliance. Cure rates of 90-95% for trichomoniasis have been reported with these recommended dosages. Treating the patient's sexual partners further improves the cure rate. Trichomonal resistance to this agent has also been reported; current resistance rates are reported at 5-10%.

If treatment with either single-dose or multidose therapy fails, a regimen of 2 g of oral metronidazole or tinidazole for 5 days may be considered. Metronidazole gel is not recommended for the treatment of trichomoniasis because therapeutic levels are not reached.

Patients should not consume alcohol during the course of treatment and for 24 hours after the last dose. The CDC currently recommends that infected symptomatic pregnant females be treated with 2 g metronidazole in a single dose. Infected asymptomatic pregnant women may wish to defer treatment to after 37 weeks' gestation.

The mode of action of metronidazole is not well understood. The drug appears to be absorbed into cells; intermediate metabolites bind DNA and inhibit protein synthesis, causing cell death.

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Tinidazole (Tindamax)

• Dosing, Interactions, etc.

Clinical Context:  Tinidazole has a longer half-life (12-14 h) than metronidazole (6-7 h). Therapy consists of a single oral 2-g dose taken with food. Reported cure rates for trichomoniasis range from 86-100%. Randomized clinical trials comparing single 2-g doses have shown metronidazole and tinidazole to be equally effective. The CDC has reported cases of metronidazole-resistant T vaginalis that was susceptible to tinidazole.

Patients on tinidazole therapy should not consume alcohol during therapy or for 72 hours after completion of the medication. Tinidazole is not recommended for the treatment of trichomoniasis in pregnant women.

Tinidazole is a 5-nitroimidazole derivative used for susceptible protozoal infections. The nitro group is reduced by a cell extract of Trichomonas. The free nitro radical generated is thought to be responsible for antiprotozoal activity against T vaginalis. The advantage of tinidazole over metronidazole is that it has fewer adverse effects, including nausea and vomiting, and may be better tolerated in a single high dose.

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Class Summary

Antiprotozoal therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. In the treatment of trichomoniasis, 5-nitroimidazole drugs are the only widely used antiprotozoal agents.^[11] 5-Nitroimidazoles are believed to disrupt the helical structure of DNA in trichomonads, ultimately leading to cell death.^[115] The exact mechanisms of many antiprotozoal agents, including 5-nitroimidazoles, are not well understood.

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